Propionitrile → HCID 68770268, compound

HRID 2109136Notes

Reaction equation

HRID 2109136 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C@H:8]([OH:24])[CH2:9][NH:10][C:11]([CH3:23])([CH3:22])[CH2:12][CH:13]2[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)=[C:4]([F:27])[C:3]=1[F:28].C(#N)CC.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.[C:55]([O:59][CH2:60][CH3:61])(=[O:58])[CH:56]=[CH2:57]>CC([O-])=O.CC([O-])=O.[Pd+2].C(N(CC)CC)C>[CH2:60]([O:59][C:55](=[O:58])/[CH:56]=[CH:57]/[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C@H:8]([OH:24])[CH2:9][NH:10][C:11]([CH3:23])([CH3:22])[CH2:12][CH:13]2[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)=[C:4]([F:27])[C:3]=1[F:28])[CH3:61]

Participants

7

Reactant 4

HCID 7854PropionitrileHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 68767490HCID 68767490, compound

Product 1

HCID 68770268HCID 68770268, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Procedure

A 150 mL sealed tube was charged with a stirring bar, (R)-1-(4-Bromo-2,3-difluorophenoxy)-3-(2-indan-2-yl-1,1-dimethyl-ethylamino)-propan-2-ol (3.06 g) 1 and propionitrile (70 mL). To this was added Pd(OAc)2 (0.151 g), P(O-tol)3 (0.82 g), ethyl acrylate (1.35 g), triethylamine (2.73 g) sequentially and deoxygenated the reaction by bubbling nitrogen for 15 minutes. The sealed tube was capped tightly and immersed into a preheated (120° C.) oil bath. The reaction was heated at this temperature for 12 hrs. Cool to ambient temperature and concentrated under reduced pressure. The crude residue was purified by flash column chromatography eluting initially with 50% EtoAc in hexanes and 100% EtOAc. At this time the eluting solvent mixtures were switched to 100% dichloromethane, 5% MeOH in dichloromethane followed by 8% MeOH in dichloromethane. The product was collected and concentrated to get the desired product (2.40 g, 75%) as pale yellow foam. MS (ES) m/z 474 [M+H]+.

Workup

  1. customA 150 mL sealed tube
  2. additionwas charged with a stirring bar
  3. customdeoxygenated
  4. customthe reaction
  5. customby bubbling nitrogen for 15 minutes
  6. customThe sealed tube was capped tightly
  7. customimmersed into a preheated (120° C.) oil bath
  8. temperatureThe reaction was heated at this temperature for 12 hrs
  9. concentrationconcentrated under reduced pressure
  10. customThe crude residue was purified by flash column chromatography
  11. washeluting initially with 50% EtoAc in hexanes
  12. customThe product was collected
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3acba324dcfd4d08aef3fc1d03d729d2
Source dataset
uspto-grants-2009_04
Patent number
US07514473B2

Reaction notes

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